Breast cancer cells respond to both steroid hormones such as estrogen and polypeptides growth factors such as insulin-like growth factor-1 (IGF-I) . Because increased IGF-I activity correlates with tumor cell aggressiveness in vitro, and may correlate with tumor responsiveness in breast cancer patients, we have investigated whether signal transduction pathways downstream from the IGF-I receptor are activated in breast cancer cells. 4 of 5 cell lines tested constitutively activate 2 kinase pathways intimately linked with the IGF-I receptor. Activation of these pathways can be exploited using pharmacologic inhibitors which cause dramatic increases in programmed cell death (apoptosis). Experiments in combination with traditional forms of therapy and other inducers of apoptosis are underway. Exploitation of IGF-I stimulated signalling is a novel approach to promote breast cancer cell apoptosis and may eventually have therapeutic implications. - apoptosis, breast cancer, signal transduction,